In the year 1614, Japan is under the rule of the Tokugawa shogunate, but a succession crisis threatens to tear the government apart. The retired shogun Tokugawa Ieyasu faces a dispute between two of his grandsons, each backed by rival factions within the court. To settle the matter without open civil war, Ieyasu revives a centuries-old conflict between two legendary ninja clans: the Kōga of Manjidani and the Iga of Tsubagakure. A fragile truce, brokered long ago by Hattori Hanzō, had kept the clans from annihilating each other, but the hatred between them never truly died. Now, that truce is dissolved. Each clan must select ten of its finest warriors to fight to the death in a proxy war. The grandson represented by the surviving clan will become the next shogun, and the winning clan will enjoy the favor of the Tokugawa for a thousand years.

The story follows Kōga Gennosuke, the young heir of the Kōga clan, and Oboro, the young heir of the Iga clan. Before the truce was broken, the two had fallen deeply in love and were betrothed to be married, hoping their union would finally end the feud between their families and bring lasting peace. Their dream is shattered when the conflict is reignited, forcing them onto opposite sides of a brutal war neither wants. Gennosuke possesses the power of the basilisk eye, a technique that reflects any killing intent back upon the attacker, causing them to destroy themselves. Oboro, though she knows no ninjutsu, possesses the innate ability called the hagengan, or occult-piercing eye, which can nullify all ninja techniques simply by looking at them. Their love is tested against the demands of duty, honor, and the survival of their clans.

The Kōga clan is led by the elderly Danjō, a master of hidden poison needles who once loved Oboro's grandmother, Ogen, the leader of the Iga. Alongside Gennosuke, the Kōga field a roster of deadly fighters: Muroga Hyōma, Gennosuke's blind uncle, who shares the basilisk eye but can only use it at night; Jimushi Jūbee, a limbless ninja who moves with serpentine speed and spits a hidden blade from his throat; Kasumi Gyōbu, who can merge into walls and solid surfaces to ambush enemies; Udono Jōsuke, an obese man whose rubbery body is impervious to physical attacks; Kazemachi Shōgen, a spider-like fighter who spits cannonball-like phlegm and moves with terrifying agility; Kisaragi Saemon, a master of disguise who can perfectly assume any face and voice; his younger sister Koi, whose skin absorbs the blood of anyone she touches; and Kagerō, a legendary beauty whose breath turns lethally poisonous when she is near a man she desires. Kagerō secretly loves Gennosuke but cannot approach him because of her deadly power, and she harbors resentment toward Oboro for winning his heart.

The Iga clan is overseen by the aged Ogen, a master of all ninjutsu. Her second-in-command is Yakushiji Tenzen, a cold and immortal schemer who can resurrect from any wound due to a parasitic creature inside his body. Alongside Oboro, the Iga forces include: Shuken, who can spray blood from her pores to create a crimson mist and ambush enemies; Amayo Jinzaburō, a man who can dissolve into liquid but will die if he touches salt; Hotarubi, a beautiful woman who controls insects and reptiles, using butterflies to create illusions and a white venomous snake as a weapon; her fiancé Yashamaru, who wields a black rope woven from treated women's hair, as sharp and strong as steel; Chikuma Koshirō, a loyal young fighter who uses twin sickles and can create miniature whirlwinds by inhaling; Azuki Rōsai, an old man with limbs that can freely stretch and contort; and Minonki, a hairy beast-like man who uses a staff and controls his thick hair as extra limbs.

The conflict begins with a burst of violence as the clan leaders, Danjō and Ogen, meet and kill each other in a mutual strike. The ten warriors on each side then engage in a series of brutal, one-on-one and small-group battles across the Japanese countryside. Each fight showcases the unique and often grotesque abilities of the combatants, with the body count rising steadily on both sides. Personal loyalties, secret loves, and old grudges complicate the struggle. Saemon uses his disguise powers to infiltrate the Iga and sow chaos. Kagerō's poisonous nature leads to tragedy. Tenzen's immortality makes him a seemingly unstoppable foe. The romance between Gennosuke and Oboro is a constant undercurrent, as both try to find a way to stop the bloodshed without betraying their clans.

In the final stages of the war, only Gennosuke and Oboro remain. The two meet on the battlefield. Oboro, unable to bring herself to kill the man she loves, turns her hagengan upon herself, committing suicide. Gennosuke, heartbroken, takes her body into a river and writes the Iga victory on the scroll with her blood before taking his own life. The war ends with no true victor, and the love between the two heirs is extinguished by the very conflict it was meant to prevent. The story is a tragic tale of duty versus love, where the ancient hatred of two clans consumes the hope for peace embodied by its youngest members.